Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells

Peripheral blood stem cells (PBSC) obtained from granulocyte-colony stimula ting factor (G-CSF)-mobilized donors are increasingly used for allogeneic t ransplantation. Despite a 10-fold higher dose of transplanted T cells, acut e graft-versus-host disease (GVHD) does not develop in higher proportion in recipients of PBSC than in recipients of marrow. T cells from G-CSF-treate d experimental animals preferentially produce IL-4 and IL-10, cytokines cha racteristic of Th2 responses, which are associated with diminished GVHD-ind ucing ability. We hypothesized that G-CSF-mobilized PBSC contain antigen-pr esenting cells, which prime T-lymphocytes to produce Th2 cytokines, Two dis tinct lineages of dendritic cells (DC) have been described in humans, DC1 a nd DC2, according to their ability to induce naive T-cell differentiation t o Th1 and Th2 effector cells, respectively, We have used multicolor microfl uorometry to enumerate DC1 and DC2 in the peripheral blood of normal donors . G-CSF treatment with 10 to 16 mu g/kg per day for 5 days increased periph eral blood DC2 counts from a median of 4.9 x 10(6)/L to 24.8 x 10(6)/L (P = .0009), whereas DC1 counts did not change. Purified DC1, from either untre ated or G-CSF treated donors, induced the proliferation of allogeneic naive T cells, but fresh DC2 were poor stimulators. Tumor necrosis factor-alpha (TNF-alpha)-activated DC1 induced allogeneic naive T cells to produce IFN-g amma, which is typical of Th1 responses, whereas TNF-alpha-activated DC2 in duced allogeneic naive T cells to produce IL-4 and IL-10, which are typical of Th2 responses. PBSC transplants contained higher doses of DC2 than marr ow transplants (median, 2.4 x 10(6)/kg versus 0.5 x 10(6)/kg) (P = .006), w hereas the dose of DC1 was comparable. Thus, it is conceivable that transpl antation of G-CSF-stimulated PBSC does not result in overwhelming acute GVH D because the graft contains predominantly Th2-inducing DC, Adoptive transf er of purified DC2 may be exploited to induce immune deviation after transp lantation of hematopoietic stem cells or organ allografts, (Blood, 2000;95: 2484-2490) (C) 2000 by The American Society of Hematology.